Hormones can influence drug addiction-A narrative review.

Drug addiction is a dangerous condition that is the concern of human societies. Nevertheless, several issues exist ahead of people with a drug use disorder during addiction. Accordingly, various types of studies have been conducted to understand better the problems that people with a drug use disorder encountered. People with a drug use disorder usually have a problem tolerating the withdrawal period and some relapse to drug abuse. Complementary studies further revealed that some hormones like oxytocin (OXT), vasopressin, hypothalamic-pituitary-adrenal axis (HPA) axis hormones, sex hormones, thyroid hormones, and nutritional hormones are probably involved in addiction processes. These hormones completely with different mechanisms can influence drug users' ultimate outcome. As we will see, these hormones influence tolerance, sensitization, and compulsive drug seeking and taking behavior. In this review, they have been further discussed.

Prostaglandins as the Agents That Modulate the Course of Brain Disorders.

Neurologic and neuropsychiatric diseases are associated with great morbidity and mortality. Prostaglandins (PGs) are formed by sequential oxygenation of arachidonic acid in physiologic and pathologic conditions. For the production of PGs cyclooxygenase is a necessary enzyme that has two isoforms, that are named COX-1 and COX-2. COX-1 produces type 1 prostaglandins and on the other hand, COX-2 produces type 2 prostaglandins. Recent studies suggest PGs abnormalities are present in a variety of neurologic and psychiatric disorders. In a disease state, type 2 prostaglandins are mostly responsible and type 1 PGs are not so important in the disease state. In this review, the importance of prostaglandins especially type 2 in brain diseases has been discussed and their possible role in the initiation and outcome of brain diseases has been assessed. Overall the studies suggest prostaglandins are the agents that modulate the course of brain diseases in a positive or negative manner. Here in this review article, the various aspects of PGs in the disease state have discussed. It appears more studies must be done to understand the exact role of these agents in the pathophysiology of brain diseases. However, the suppression of prostaglandin production may confer the alleviation of some brain diseases.

Reduction of anxiety level is associated with an oxidative-stress imbalance in the hippocampus in morphine administration period in male rats.

Hippocampus is a region of the brain that is famous for its role in memory. However recently it has been given great importance for a region that regulates emotion and anxiety. Alternation of anxiety level has been observed in drug abusers as a comorbid disorder. The aim of this study is to show that morphine by altering oxidative stress in the hippocampus causes anxiety level alternation. In this study 32 male Sprague-Dawley rats divided into four groups: Control, N-acetyl-cysteine-treated, morphine-treated and N-acetyl-cysteine + morphine-treated. After 14 days of morphine administration (5 mg/kg/rat/i.p.) and N-acetyl-cysteine administration (100 mg/kg/rat/i.p.), Anxiety was assessed with Elevated Plus Maze (EPM) after 14 days in all groups. Then rats were euthanized and the hippocampus was removed for assessing oxidative stress for malondialdehyde (MDA), glutathione and nitrite/nitrate. Our data showed that oxidative stress was disturbed in the hippocampus in morphine-treated rats. Malondialdehyde (MDA) increased and glutathione and nitrite/nitrate were reduced in morphine-treated rats compared to control and N-acetyl-cysteine-treated rats. N-Acetylcysteine treatment improved oxidative stress (OS) markers and anxiety. The anxiety that was assessed with Elevated Plus Maze, morphine-treated rats showed less anxiety level compared to N-acetyl-cysteine -treated and control rats. Morphine reduced the anxiety level. The reduction of anxiety level was associated with oxidative stress imbalance in the hippocampus. Thus, hippocampus can alter anxiety level.

Paradoxical regulation of iron in hippocampus and prefrontal cortex induces schizophrenic-like symptoms in male rats.

Introduction: Social isolation induces schizophrenic-like symptoms. Iron is an essential element for brain functions. The aim of this study is to investigate if the emergence of schizophrenia after social isolation is the result of impaired iron metabolism in the hippocampus and in the prefrontal cortex.Methods and materials: In this study, 42 male Sprague-Dawley rats were randomly divided into six groups: 1) grouped housed (GH), 2) socially isolated (SI), 3) grouped housed + vehicle, 4) grouped housed + morphine, 5) socially isolated + vehicle and 6) socially isolated + morphine. After 14 days of social isolation and group housing, behavioral experiments were performed. Then, the iron in the hippocampus, prefrontal cortex, and serum was assessed.Results: SI rats were more anxious in compared to GH rats. Memory was better in GH rats compared to SI rats. SI rats had more locomotor activity compared to GH rats. Iron was higher in the hippocampus in GH rats compared to SI rats. Paradoxically iron was higher in the prefrontal cortex in SI rats compared to GH rats. In serum, iron was higher in GH rats compared to SI rats.Conclusion: Emergence of schizophrenic-like symptoms is associated with the paradoxical concentration of iron in hippocampus and prefrontal cortex in the isolation period. Further studies are recommended to investigate the possible specific changes in ion transporters and the metabolism of the neurotransmitter that occurs as the result of this paradoxical regulation.

Modulation of catalase, copper and zinc in the hippocampus and the prefrontal cortex in social isolation-induced depression in male rats.

Depression is a chronic illness of unknown etiology. Trace elements, such as copper and zinc, and defense antioxidants, such as catalase, are important factors that determine the clinical course of brain diseases. Furthermore, altered glucose metabolism in hippocampus and prefrontal cortex has been associated with depression. Identifying factors that can precipitate depressive-like behavior is of particular importance as it can direct clinicians towards the etiology of the disease. In this study, 16 male Sprague-Dawley rats were randomly divided into two groups: socialized and socially isolated. After one week of acclimatization, animals were housed in isolation for 14 days. Rats in the social group were socialized together for 14 days. On day 15, the forced swim test was performed and blood sugar was analyzed. The brain was removed immediately for biochemical analysis. Socially isolated rats showed more pronounced depressive-like behavior in the forced swim test than socialized rats. Moreover, socially isolated rats demonstrated significantly lower copper and zinc concentrations, as well as a marked reduction in catalase activity, in both prefrontal cortex and hippocampus compared to socialized rats. Additionally, blood sugar levels were higher in socially isolated animals. Isolation causes reduction in copper and zinc levels and catalase activity, which may precipitate depressive-like behavior in these animals.

Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview.

Neuropsychiatric and neurologic diseases cause a great burden for individuals, families, and societies. Social isolation rearing can trigger a variety of psychiatric diseases. New advances suggest that epigenetic factors along with other neurochemical changes can be an important topic in neuropsychiatric diseases. It is thought that the prevention of social isolation rearing that occurs around birth can reduce the occurrence of neuropsychiatric diseases. It has been suggested that the environment can induce epigenetic alternation. So, for the diagnosis of a proportion of neuropsychiatric diseases, assessing epigenetic factors may be helpful. Also, apart from epigenetic factors, new advances have been made about new mechanisms of and treatments for such a disorder.

Co-Administration of Progesterone and Melatonin Attenuates Ischemia-Induced Hippocampal Damage in Rats.

Stroke is the second leading reason for death worldwide and is one of the fundamental causes of long-term disabilities. The aim of this investigation was to assess the impact of combined administration progesterone (PROG) and melatonin (MEL) on stroke complications. Male Wistar rats (9-10 weeks) weighing 250-300 g were used as a part of this examination. They were randomly separated into eight groups (nine rats for every group). Common carotid arteries on the two sides clamped (BCCAO model) with non-traumatic clips for 20 min. At that point, the rats were treated with 8 mg/kg PROG, 10 mg/kg MEL, and vehicles (sesamoid and normal saline). Morris water maze testing was performed following 2 weeks. At that point, the rats were euthanized, and histological examination was directed. The outcome demonstrated that utilization of PROG and MEL in treatment groups essentially increases the quantity of pyramidal cells and enhances spatial memory compared to non-treatment groups (p < 0.05). Moreover, the neuroleptic factor gene expression and protein concentration were significantly enhanced in the treated groups (p < 0.05). As indicated by the outcomes, co-administration of PROG and MEL can enhance learning and memory by surviving the pyramidal neurons and diminishing neural death by means of increasing neuroleptic factors in the hippocampal CA1 zone.

Overview of the Recent Advances in Pathophysiology and Treatment for Autism.

BACKGROUND & OBJECTIVE: Autism is a developmental disorder that manifests itself in early childhood. Autism is characterized by inability to acquire social skills, repetitive behaviors and failure of speech and nonverbal communication development. Recent studies have shown that genetic mutations occur in majority of individuals with autism. These mutations cause a variety of disorders that ultimately lead to brain disorders. It is noteworthy that all mutations do not follow the same pattern. They encompass various kinds of mutations. Autism needs to be treated during childhood as untreated patients usually do not progress to the later stages of development. In this regard, many studies have been performed and numerous treatments have been proposed to improve the outcome of this disease. CONCLUSION: In this review, we have discussed new advancements made in understanding the pathophysiology of autism. Furthermore, we have also discussed new treatments which have been proposed and have successfully translated affected children. Overall, it is concluded that new advances have largely helped these patients.

Socialization Alleviates Burden of Oxidative-Stress in Hippocampus and Prefrontal Cortex in Morphine Addiction Period in Male Rats.

INTRODUCTION: Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction of high-risk behaviors can reduce the burden of addiction in society and can improve the overall prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with socialization will reduce occurrence of high-risk behavior during addiction period. METHOD: Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized, isolated, addicted socialized and addicted isolated. For inducing morphine dependence, rats received morphine (5 mg/rat/kg/day) for 14 days. Socialization was induced by putting two rats in a large cage for 14 days. On the other hand, isolation was induced by putting rats in separate small cages covered with black plastic for the same period. At the end of the study, rats were experimented with shuttle box for assessing avoidance memory and also tested with social interaction test to measure noveltyseeking behavior and anxiety level. Then, animals were sacrificed for neurochemical analysis. Brain was isolated to assess oxidative-stress (OS) indices such as malondialdehyde (MDA), glutathione and nitrite/nitrate in prefrontal cortex and hippocampus. RESULTS: After 14 days of morphine injection, rats in socialized group had improved avoidance memory, increased anxiety levels and reduced novelty-seeking behavior. Furthermore, isolated rats had reduced glutathione and nitrite/nitrate, and higher MDA levels in prefrontal cortex and hippocampus as compared to socialized rats. CONCLUSION: Pair state had positive effect on OS indices in prefrontal cortex and hippocampus and results in the reduction of relapse and poor prognosis. Thus, OS plays an important role in alleviation of severity of addiction period.

Assessment of Improvement in Oxidative Stress Indices with Resocialization in Memory Retrieval in Y-Maze in Male Rats.

INTRODUCTION: Memory deficit is an important issue in some psychiatric diseases either as a primary symptom or as a comorbid symptom. Factors that determine the decline or improvement of memory are an important subject to reduce the severity of these diseases. METHODS AND MATERIALS: In this study, 32 male Sprague-Dawley rats were randomly divided into 4 experimental groups: social (control), isolation, resocialization for 3 days, and resocialization for 7 days. Isolation occurred for 14 days. Resocialization groups were resocialized for 3 or 7 days after isolation. In the social group, there was no intervention with normal socializing among the rats. In the isolation group, rats were isolated with no resocialization. In all 4 groups, after performing the Y-maze, the rats' brains were removed to assess oxidative stress status in the hippocampus and prefrontal cortex. RESULTS: Y-maze performance improved after 3 and 7 days of resocialization. However, oxidative stress status for malondialdehyde, glutathione and nitrite/nitrate returned to normal levels except in 2 experiments after 7 days of resocialization. In addition, in 2 experiments, just glutathione in the prefrontal cortex and nitrite/nitrate in the hippocampus after 3 days of resocialization improved. CONCLUSIONS: A return to normal levels in all types of antioxidant markers in the resocialization groups is not the only factor for improving memory deficits resulting from isolation. Resocialization may also be activating other regulatory mechanisms besides an antioxidant defense.

Deficit in Memory Is Associated with Paradoxical Regulation of Magnesium and Manganese in Isolated Male Rats.

BACKGROUND: Magnesium (Mg) and manganese (Mn) play an important role in brain development and glutathione, the master antioxidant in the brain, is necessary for the cognitive function. This study is aimed at determining the effect of magnesium and manganese concentrations in hippocampus and prefrontal cortex on the glutathione function. The reduction in glutathione leads to memory impairment in -Y-maze in the isolation period. METHODS: In this study, 16 male Sprague-Dawley rats were randomly divided into 2 groups: social and isolation. Based on previous studies, the isolation period was considered as 14 days, plus 1 week for acclimatization. On day 15, after assessing the memory with Y-maze, rats were examined for glutathione in serum, hippocampus, and prefrontal cortex. Also, serum, hippocampus, and prefrontal cortex were obtained for assessing Mn and Mg. RESULTS: The memory in Y-maze was impaired in isolated rats. Also, glutathione in hippocampus and prefrontal cortex was reduced in isolated rats versus socialized rats. In serum assay, glutathione reduced in socialized rats versus isolated rats. Mg was reduced in isolated rats versus socialized rats in serum assay. Paradoxically, Mn was increased in isolated rats versus socialized rats in serum assay. In tissue assay, Mg in hippocampus increased in socialized rats versus isolated rats. Paradoxically, in prefrontal cortex Mg increased in isolated rats versus socialized rats. Mn in hippocampus showed increased concentration in socialized rats versus isolated rats. Paradoxically, Mn showed reduced concentration in prefrontal cortex in socialized rats versus isolated rats. CONCLUSION: Manganese and magnesium are necessary elements for maintaining enough level of cognition in the isolation period. Also, glutathione plays an important role.

The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia.

Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks) used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR), vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract). Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001). Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001). Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

Simvastatin enhances the hippocampal klotho in a rat model of streptozotocin-induced cognitive decline.

Brain oxidative status is a crucial factor in the development of sporadic Alzheimer's disease (AD). Klotho, an anti-aging protein, diminishes oxidative stress by the induction of manganese superoxide dismutase (MnSOD). Thus, the substances that increase klotho expression could be considered as a potential treatment for Alzheimer's disease when the oxidative imbalance is present. Statins are suggested to up-regulate klotho expression. We examined the effect of simvastatin (5mg/kg, daily for 3weeks) on hippocampal klotho and MnSOD expression in the cognitive declined animal model induced by intracerebroventricular (ICV)-streptozotocin (STZ) administration. Cognitive assessment was performed by the Morris Water Maze (MWM) test. The results indicated that mean escape latency and distance were prolonged in the ICV-STZ group compared with the control group. The expression of klotho and MnSOD were also down regulated in the hippocampus. Furthermore, improved spatial performance was observed in simvastatin-treated animals. This effect could be related to increase in oxidative stress tolerance as evidenced by klotho and MnSOD up-regulation. Our current study indicates that klotho upregulation may be a neuroprotective mechanism of simvastatin against cognitive decline in AD.

Study of the effects of controlled morphine administration for treatment of anxiety, depression and cognition impairment in morphine-addicted rats.

BACKGROUND: Morphine dependency usually results in undesired outcomes such as anxiety, depression, and cognitive alterations. In this study, morphine was used to manage morphine dependence-induced anxiety, depression, and learning and memory disturbances. MATERIALS AND METHODS: Forty rats were divided equally into five groups. Group 1 received saline for 21 days. Groups 2-5 were dependent by increasing administration of morphine (15-45 mg/kg) for 7 days. For the next 14 days, morphine was administered as the following regimen: Group 2: once daily; 45 mg/kg (positive controls), Group 3: the same dose with an increasing interval (6 h longer than the previous intervals each time), Group 4: the same dose with an irregular intervals (12, 24, 36 h intervals interchangeably), and Group 5: decreasing doses once daily (every time 2.5 mg/kg less than the former dosage). On days 22-26, elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were performed to investigate anxiety level and depression in animals. Between 17th and 21st days, Morris water maze (MWM) was used to evaluate the spatial learning and memory. RESULTS: Chronic morphine administration caused depression and anxiety as observed by FST, EPM, and TST and decreased motor activity in OFT and caused impairment in learning and memory performance in MWM. Treatment with our protocol as increasing interval, irregular interval, and decreasing dosage of morphine caused marked reduction in depression, anxiety, and improved cognition performance compared with positive control group; and attenuated motor deficits in morphine-dependent rats, remarkably. CONCLUSIONS: Change in dosage regimens of morphine can reduce morphine-induced anxiety, depression, and cognitive impairments.

Synergistic Effects of Social Isolation and Morphine Addiction on Reduced Neurogenesis and BDNF Levels and the Resultant Deficits in Cognition and Emotional State in Male Rats.

INTRODUCTION: Addiction to drugs of abuse is a devastating condition which results in deterioration of brain function. On the other hand, social isolation also produces cognitive deficits such as learning and memory impairment. This study was designed to evaluate the potential negative synergistic effects of social isolation and morphine addiction on brain functions. METHODS AND MATERIAL: One hundred and two Sprague-Dawley rats were randomly divided into four groups for assessing neurogenesis and behaviour: group-housed, isolated, morphine-treated group-housed and morphine-treated isolated groups. Morphine- treated animals received BrdU (50 mg/kg; i.p.) and Morphine (0.75 mg/rat; i.p.) for 14 consecutive days, whereas, control rats received BrdU (50 mg/kg; i.p.) only. At the end of the study, Morris water maze and elevated plus maze tasks were performed to assess spatial working memory and anxiety levels, respectively. Furthermore, neurogenesis and BDNF levels were studied. RESULTS: Reference and working memory was markedly impaired in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Neurogenesis and BDNF levels were reduced in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Furthermore, rats in both isolated groups demonstrated low anxiety levels when compared to group housed groups. CONCLUSION: Isolation during addiction imparts devastating effects on brain. Thus, socialization of addicts can minimize addiction - induce cognitive deficits and improve neurogenesis.

Protective effects of forced exercise against nicotine-induced anxiety, depression and cognition impairment in rat.

BACKGROUND: Nicotine is one of the psychostimulant agents displaying parasympathomimetic activity; the chronic neurochemical and behavioral effects of nicotine remain unclear. Exercise lowers stress and anxiety and can act as a non-pharmacologic neuroprotective agent. In this study, the protective effects of exercise in nicotine withdrawal syndrome-induced anxiety, depression, and cognition impairment were investigated. METHODS: Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control and received normal saline (0.2 mL/rat, i.p.) for 30 days, whereas group 2 (as positive control) received nicotine (6 mg/kg/day, s.c.) for the first 15 days. Groups 4, 5, and 6 were treated with nicotine (6 mg/kg/day, s.c.) for the first 15 days and then were treated with forced exercise, bupropion (20 mg/kg/day, i.p.), or a combination of the two for the following 15 days. Between day 25 and day 30, Morris water maze was used to evaluate spatial learning and memory. From days 31 to 35, the elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were used to investigate the level of anxiety and depression in the subjects. RESULTS: Nicotine-dependent animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM, and TST, which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. CONCLUSIONS: Forced exercise, bupropion, or their combination can attenuate nicotine cessation-induced anxiety, depression, and motor activity in the mentioned behavioral assay. We conclude that forced exercise can protect the brain against nicotine withdrawal-induced anxiety, depression, and cognitive alteration.

Protective effects of various dosage of Curcumin against morphine induced apoptosis and oxidative stress in rat isolated hippocampus.

BACKGROUND: During recent years, the defensive role of Curcumin against oxidative stress and apoptosis has been experimentally documented. Long term consumption of morphine induces apoptosis and oxidative stress which may cause serious damage to brain cells. To investigate whether Curcumin could protect rat's hippocampus against morphine induced destruction, we assessed isolated hippocampus cells for oxidative stress, anti oxidant factor and apoptotic factor activities. METHODS: For this, 40 adult male rats were taken and randomly allocated to one of the five groups. Groups 1 and 2 received morphine (45 mg/kg) and normal saline (0.2 ml/rat) respectively for four weeks. Groups 3, 4 and 5 concurrently were treated with morphine (45 mg/kg, sc) and Curcumin (10, 20 and 40 mg/kg) for four weeks. RESULTS: The results showed that morphine significantly increased lipid peroxidation, mitochondrial GSH level, concentration of Bax; caspase-3 and caspase-9 activities while decreasing Bcl-2 concentration. Further, a significant decrease in superoxide dismutase and glutathione peroxidase activity was also observed. Various dosage of Curcumin attenuated these effects by significantly lowering lipid peroxidation, GSSG level, Bax concentration, caspase-3 and caspase-9 activities, while increasing superoxide dismutase and glutathione peroxidase activity, GSH level and Bcl-2 concentration. CONCLUSIONS: These findings have demonstrated that Curcumin can act as an antioxidant and antiapoptotic agent against damage induced by morphine dependence.

Hippocampal DHCR24 down regulation in a rat model of streptozotocin-induced cognitive decline.

The DHCR24 (24-dehydrocholesterol reductase) gene codes a multifunctional protein which consists of enzymatic, antioxidant, and anti-apoptotic activities. It exists in almost all neurons and protects the neural cells against amyloid ß toxicity. Several studies have shown the down regulation of DHCR24 in Alzheimer's disease. We examined the time profile of DHCR24-mRNA alteration in an animal model of streptozotocin (STZ)-induced cognitive impairment. The DHCR24 mRNA levels of hippocampus and cognitive impairment were evaluated at 7, 14, and 21 days after intracerebroventricular (ICV)-STZ/Saline administration. DHCR24 expression was down regulated at 14 and 21 days after ICV-STZ administration. The decrease in expression of DHCR24 preceded the onset of the cognitive impairment. These results suggest the potential relation between DHCR24 expression and cognitive impairment.

Elevated CSF and plasma microparticles in a rat model of streptozotocin-induced cognitive impairment.

Alzheimer's disease (AD), can be described as a vascular disorder, is characterized by endothelial and platelet activation. One feature of activated cells is loss of lipid asymmetry, and membrane blebbing which cause microparticle (MP) formation. MPs increased under many pathological states and little information is available relating to their changes in AD. The purpose of this work was to characterize the time course of the endothelial-derived microparticles (EMPs) and platelet-derived microparticles (PMPs) alteration after intracerebroventricular (ICV) injection of streptozotocin (STZ). Rats were injected bilaterally with ICV-STZ/Saline, cerebrospinal fluid (CSF) and plasma EMPs (Annexin V(+) CD61(-)CD144(+)) and PMPs (Annexin V(+) CD61(+)CD144(-)) were analyzed with flow cytometry at 2 h, 4 h, 24 h, 4 days, 7 days, 14 days and 21 days after ICV-STZ/Saline administration. Cognitive impairment, malondialdehyde (MDA) level of hippocampus, plasma serotonin, and serum S100B were also assessed. We showed the elevation of CSF and plasma level of EMPs and PMPs, which may represent a proinflammatory and prothrombotic status. These alterations were simultaneous with the hippocampal MDA rise, plasma serotonin increment, and S100B decrement, 7 days after ICV-STZ administration and precede the onset of cognitive impairment. Understanding the profile of MP changes in CSF or plasma as biomarkers from tissues undergoing activation or damage, may be helpful in prediction or early diagnosis of AD.